Abstract
Background: Prompt access tosuitable hematopoietic stem cells is a prerequisite for effective allograft. Availability of HLA-matched URD &CB graftscan be a major barrier to allogeneic transplantation for minority patients. Whether this limitation is improving with increasing registry size & CB inventory is not established.
Methods: From 10/2005-5/2016, we prospectively evaluated the availability of 7-8/8 HLA-allele matched URDs or 4-6/6 HLA-A,-B antigen, -DRB1 allele matched CB grafts by recipient ancestry in patients with hematologic malignancies without HLA-identical related donors. At our center, 8 HLA-allele matched URDs are given priority if available; otherwise HLA-mismatched URDs or CB grafts (predominantly double-unit) are chosen. Acceptable CB grafts have a TNC dose > 1.5 x 107/kg/unit (> 2.5 x 107/kg for single unit grafts) & 4-6/6 donor-recipient HLA-match.
Results: Of the 1,112 patients, 597 (54%) received 8/8 URD & 182 (16%) received a 7/8 URD transplant, 281 (25%) underwent CB transplant (278 with double-unit grafts) & 52 (5%) had no 7-8/8 URD or CB graft. The distribution of 1,112 8/8 URD, 7/8 URD, CB transplants & no 7-8/8 URD/ CB grafts by recipient ancestry is shown (Figure). The majority (66%) of Europeans received an 8/8 URD whereas the majority of non-Europeans (60%) received either a mismatched URD or CB graft. Southern Europeans were less likely to have an 8/8 URD than other Europeans (38% vs 71%, p < 0.001). Only one-third (36%) of non-European, non-African patients had an 8/8 URD & only 12% of African ancestry patients did (p < 0.001). CB significantly extended transplant access to all patients especially southern & non-Europeans. However, over the decade,24% of African patients had no graft as compared to only 1% of European patients (p < 0.001) and 6% of non-European non-African patients (p < 0.001).When the origin of CB grafts was analyzed, we found that 68% of CB units for European ancestry patients were from domestic U.S. banks whereas in non-European non-African & African patients 72% & 84% of CB units were obtained from the US inventory, respectively (p = 0.006).
To determine if donor access is improving, we then analyzed transplant type (or no URD/CB graft) by recipient ancestry in the last 4 years (recent period 5/2012-5/2016, n = 521) vs the earlier time period (10/2005-4/2012, n = 591) (Table). For this analysis, all non-southern Europeans were grouped. In recent years, disparity in graft access between ancestry groups persists. For example, in recent patients 40% of southern Europeans, 78% of other Europeans, 41% of non-African non-Europeans & only 19% of Africans received an 8/8 URD transplant (p < 0.001). Furthermore, recent no URD/CB graft rates were < 2% in all Europeans, 5% in non-European non-Africans but remained 19% in African patients (p < 0.001). Finally, comparing the recent 4 years to the earlier period, the decrease in the no URD/CB graft rate for African patients (19% vs 29%) was not significant (p = 0.212).
Conclusion: Despite increasing URD registry/ CB inventory size, significant racial disparity persists in access to matched URDs. CB significantly extends transplant access especially to southern & non-European patients. In recent years, however, while 46% of African patients have received a CB graft, a significant number of these patients remain without a 7-8/8 URD or CB graft. Whilehaplo-identical donors offer an additional alternative graft source, the extension of minority patient transplant access using domestic CB units supports the importance of public CB bank funding especially for African patients and those without suitablehaplo-identical donors.
Distribution of 7-8/8 URD & CB transplants & no 7-8/8 URD/ CB grafts by patient ancestry.
Distribution of 7-8/8 URD & CB transplants & no 7-8/8 URD/ CB grafts by patient ancestry.
Transplant type according to patient ancestry by time period: 10/2005-4/2012 (early period) vs 5/2012-5/2016 (recent period).
Transplant type according to patient ancestry by time period: 10/2005-4/2012 (early period) vs 5/2012-5/2016 (recent period).
No relevant conflicts of interest to declare.
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